George King, MD

FocusClinical Therapeutics

ADA Research FundingMentor-Based Fellowship, Sponsored by Z Gallerie/Zeiden Family

In 1948, about 25 years after the development of insulin for treating diabetes, pioneering diabetes researcher Elliott Joslin, MD, began giving medals to patients who had survived a quarter century with the disease. Joslin died in 1962, but the Boston clinic he founded kept up the tradition: In 1970, it awarded its first 50-year medals. And in 1996, the Joslin Diabetes Center recognized the first person to live with diabetes for 75 years.

Since bestowing that first 50-year medal, the center has tracked nearly 3,000 patients, each with at least a half century of experience coping with diabetes. The awards are more than just something to be very proud of. They’re also a way for scientists to help thousands of others beat the disease. The idea is simple: Learn what makes Joslin medalists so long-lived, and see if it can be distilled somehow and applied to others.

Joslin researcher George King, MD, is one of the people using data gathered from 50-year medalists (nearly 900 of them) to search for a cure. King is especially interested in an even smaller group, a subset of the study participants who never developed eye, kidney, or heart complications in a half century or more of living with diabetes.

Their experience is unusual. Typically, long-duration diabetes patients “get a lot of complications, generally related to glucose, lipids, and insulin resistance,” King says. “Our work has been looking at how glucose and insulin resistance are causing these complications, but finding real treatments has been difficult.”

King and others at Joslin are hoping years of data and research on Joslin medalists can change that. For nearly a decade, researchers have studied medalist volunteers extensively, both before and after they die. “The difficult part of studying complications is it involves organs that are difficult to be separated from while you’re alive—eyes, heart, kidneys,” King says. “Some people have been kind enough to donate tissues. We do studies and see which might be potentially helpful.”

The research has revealed some surprises. For example, studying dozens of donated pancreases showed that some of the medalists still had functioning beta cells more than 50 years after their initial diagnosis. “Some of these medalists [were] still producing insulin,” King says.

King’s now looking for ways the medalists might somehow have been protected from complications by the way their bodies dealt with diabetes over the years. He’s zeroed in on cardiovascular disease, a major cause of death in people with diabetes. Most women with diabetes, for example, have higher rates of cardiovascular disease, experiencing things like heart attacks and strokes more often than average.

But to King’s surprise, the women in the medalist population actually had a lower risk of heart attacks and strokes compared with men who were medalists. “We ask the question of the medalist population: Why do females retain their protection? Their HDL [‘good’ cholesterol] seems to be much higher. The question is why that is,” King says.

With the help of a grant from the American Diabetes Association, King and researcher Kyoungmin Park are experimenting to see what’s going on. “Insulin may be protecting blood vessels from cardiovascular disease,” King says. “Maybe insulin is acting differently in these people’s blood vessels, so the question is how insulin is doing that.”

If there are forces at work that can be isolated, King and Park will test them out in mice bred to produce no insulin, simulating type 1 diabetes. If the mice benefit, then the researchers will try to reverse-engineer what’s going on to develop treatments for humans. Says King: “We are trying to understand why, rather than just how. That’s a lot more helpful.”

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